This application is a competing renewal for an institutional research training program on the "Genetic Aspects of Alcoholism." Among the institutional training grants funded by NIAAA, our training program is one of five devoted to genetics of alcoholism. The main focus of research training is on the genetic, biological, and molecular basis of high alcohol-seeking behavior. Major topics of research include: neuronal mechanisms responsible for the reinforcing effects of ethanol; the genetics of alcohol metabolizing enzymes and receptors related to neurotransmission; the genetics (including QTL and finer mapping analyses) of alcohol preference and correlated phenotypes in selectively bred rat and mouse lines; studies of factors that regulate the expression of genes relevant to alcoholism; analysis of the extent that genetically-influenced biobehavioral factors such as disinhibition/impulsivity and acute tolerance/insensitivity contribute to alcoholism risks in selectively bred rodents and in human populations; and the use of an alcohol clamp method to assess the effects of genetics (MZ twins and FHP vs FHN subjects) and recent drinking history on electrophysiologic, neuroendocrine, and subjective assessment of alcohol experience. Other topics of interest include; structure and function of mutated forms of alcohol and aldehyde dehydrogenases; the relationship of ethanol exposure to retinoid metabolism, the effect of ethanol on lipoprotein metabolism; and neurodevelopmental abnormalities of fetal alcohol syndrome in mouse and rat models. One major strength of our training program is the long history of collaboration with both M.D.S. and PhDs in research and research training and the involvement of multiple scientific disciplines. A number of important resources are available to foster research training; the selective bred P/NP, HAD/LAD, HARF/LARF rat lines and the HAP/LAP mouse lines that differ in alcohol preference, a large collection of DNA samples extracted from different human populations relevant for genetic studies of alcoholism and alcohol-related end-organ injuries, and NIAAA-funded Alcohol Research Center (Molecular Biology Core, Animal Production Core, Structural and Cellular Biology Core, Mouse Selective Breeding Component, and two Human Genetics Cores, a group of IRPG grants (they replaced a former Program Project grant) that focuses on identification of genes and neurobiological mechanisms underlying high alcohol seeking behavior through studies of the HAD/LAD and P/NP rats, and the participation as one of six sites for the "Collaborative Studies on the Genetics of Alcoholism (COGA)." The trainees for each year will include five predoctoral, five postdoctoral fellows (with one M.D. and four Ph.D. trainees), and six undergraduate students on short-term training during their summer or "off quarter". Training will be through an apprenticeship mode but seminars, research conferences and hands-on method courses are amply available.